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Structure. 2015 Apr 7;23(4):688-99. doi: 10.1016/j.str.2015.01.019. Epub 2015 Mar 5.

Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily.

Author information

1
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA. Electronic address: suressl@indiana.edu.
2
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
3
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
4
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA; Departments of Neurology and Neurological Sciences, Photon Science, and Structural Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: brunger@stanford.edu.

Abstract

C1q-like (C1QL) -1, -2, and -3 proteins are encoded by homologous genes that are highly expressed in brain. C1QLs bind to brain-specific angiogenesis inhibitor 3 (BAI3), an adhesion-type G-protein coupled receptor that may regulate dendritic morphology by organizing actin filaments. To begin to understand the function of C1QLs, we determined high-resolution crystal structures of the globular C1q-domains of C1QL1, C1QL2, and C1QL3. Each structure is a trimer, with each protomer forming a jelly-roll fold consisting of 10 β strands. Moreover, C1QL trimers may assemble into higher-order oligomers similar to adiponectin and contain four Ca(2+)-binding sites along the trimeric symmetry axis, as well as additional surface Ca(2+)-binding sites. Mutation of Ca(2+)-coordinating residues along the trimeric symmetry axis lowered the Ca(2+)-binding affinity and protein stability. Our results reveal unique structural features of C1QLs among C1q/TNF superfamily proteins that may be associated with their specific brain functions.

PMID:
25752542
DOI:
10.1016/j.str.2015.01.019
[Indexed for MEDLINE]
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